1. Field of the Invention
The present invention relates to molecules that are capable of inhibiting angiogenesis, to compositions comprising one or more of the molecules, to the use of such molecules in the treatment of carcinoma, in particular solid tumors carcinomas, and to method for providing molecules that are capable of inhibiting angiogenesis.
2. Related Technology
Angiogenesis, the formation of new blood vessels from the pre-existing vasculature is fundamental to wound healing, reproduction and embryonic development. Angiogenesis is also essential for the development of tumors. New blood vessels in tumors provide nutrients allowing the cells to undergo uncontrolled mitosis.
During angiogenesis, endothelial cells proliferate, migrate into new tissue and form inter-endothelial junctions leading to tube formation. This process starts and is driven by angiogenic factors. The signalling of VEGFs and angiopoietins leads to loosening of the pericyte-endothelial contact permitting proliferation and interaction of new endothelial cells with the extracellular matrix mediated by integrins. The ανβ3 and ανβ5 integrins have been described to participate in blood vessel development and angiogenesis via a signalling crosstalk with angiogenic factors.
In addition to interactions between endothelial cells and the extra-cellular matrix, the regulation of inter-endothelial contacts is important for tube formation. For example, the adhesion molecule VE-cadherin plays a role in vascular remodelling and maintains integrity of blood vessels.
In the research that led to the present invention the junctional adhesion molecules (hereafter JAM) JAM-B and JAM-C were discovered. These molecules are found in vascular cell-cell contacts and are involved in leukocyte transendothelial migration. Now it was found that the interaction between JAM-B and JAM-C also plays an important role in angiogenesis.